Conventional laparoscopic and robotic laparoscopic techniques are both rapidly growing practices in the fields of colorectal and gynecologic surgery. Recent studies as described in Simorov et al., “Laparoscopic colon resection trends in utilization and rate of conversion to open procedure: a national database review of academic medical centers” Ann Surg. 2012 256(3), 462-468; Wright et al., “Robotically assisted vs laparoscopic hysterectomy among women with benign gynecologic disease” JAMA 2013 309(7), 689-698; and, Park et al., “Ureteral injury in gynecologic surgery: a 5-year review in a community hospital” Korean J Urol. 2012 53(2), 120-125, report 42% of all colorectal resections and greater than 30% of gynecologic procedures are attempted in this manner.
A laparoscopic approach offers several advantages over traditional open abdominal surgery, including decreased postoperative pain, shorter hospital length of stay, fewer surgical site infections, and decreased overall hospital cost, as described in Kiran et al., “Laparoscopic approach significantly reduces surgical site infections after colorectal surgery: data from national surgical quality improvement program” J Am Coll Surg. 2010 211(2) 232-238; Bilimoria et al., “Laparoscopic-assisted vs. open colectomy for cancer: comparison of short-term outcomes from 121 hospitals” J Gastrointest Surg. 2008 12(11) 2001-2009; Juo et al., “Is Minimally Invasive Colon Resection Better Than Traditional Approaches?: First Comprehensive National Examination With Propensity Score Matching” JAMA Surg. 2014 149(2) 177-184; Wilson et al., “Laparoscopic colectomy is associated with a lower incidence of postoperative complications compared with open colectomy: a propensity score-matched cohort analysis” Colorectal Dis. 2014 16(5) 382-389; Kobayashi et al., “Total laparoscopic hysterectomy in 1253 patients using an early ureteral identification technique” J Obstet Gynaecol Res. 2012 38(9) 1194-1200; Makinen et al., “Ten years of progress—improved hysterectomy outcomes in Finland 1996-2006: a longitudinal observation study” BMJ Open 2013 3(10) e003169.
However, limited tactile sensation and two-dimensional images can lead to iatrogenic ureter injury. Although infrequent, laparoscopic ureter injury remains a serious complication with significant associated morbidity. Reports indicate an incidence between 0.1-7.6% for colorectal and gynecologic surgery with more than 80% of these failing to be recognized intraoperatively, as described in Park et al.; Palaniappa et al., “Incidence of iatrogenic ureteral injury after laparoscopic colectomy” Arch Surg. 2012 147(3), 267-271; and, da Silva et al., “Role of prophylactic ureteric stents in colorectal surgery” Asian J Endosc Surg. 2012 5(3), 105-110. Current techniques for intraoperative ureter identification include ureteral stent placement, x-ray fluoroscopy, and visible dyes; however, both stents and fluoroscopy carry additional risk to the patient, and visible dyes are often not sensitive, as described in Tanaka et al., “Real-time intraoperative ureteral guidance using invisible near-infrared fluorescence” J Urol. 2007 178(5), 2197-2202; Bothwell et al., “Prophylactic ureteral catheterization in colon surgery. A five-year review” Dis Colon Rectum. 1994 37(4), 330-334; Wood et al., “Routine use of ureteric catheters at laparoscopic hysterectomy may cause unnecessary complications” J Am Assoc Gynecol Laparosc. 1996 3(3), 393-397; and, Brandes et al., “Diagnosis and management of ureteric injury: an evidence-based analysis” BJU Int. 2004 94(3), 277-289.
Fluorescence imaging using cyanine dyes is a rapidly emerging field to support surgical navigation and provide real-time illumination of anatomic structures. Emissions in the 700-900 nm range may avoid interference from tissue auto-fluorescence and can penetrate approximately 1 cm of tissue, as described in Adams et al., “Comparison of visible and near-infrared wavelength-excitable fluorescent dyes for molecular imaging of cancer” J Biomed Opt. 2007 12(2), 024017; and, Keereweer et al., “Optical Image-Guided Cancer Surgery: Challenges and Limitations” Clin Cancer Res. 2013 19(14), 3745-3754.
Another application of fluorescence imaging is for the real-time intra-operative imaging of the biliary anatomy, including the biliary duct and cystic duct. Current methods often use indocyanine green (ICG) dye by either intra-biliary injection or intravenous injection before surgery. However, studies have shown clear problems in using ICG dye. These include poor efficiency and kinetics of excretion into bile (Tanaka et al., “Real-time intraoperative assessment of the extrahepatic bile ducts in rats and pigs using invisible near-infrared fluorescent light” Surgery 2008 144(1) 39-48) and adverse reaction with the patient (Benya et al., “Adverse reactions to indocyanine green: a case report and a review of the literature” Cathet Cardiovasc Diagn. 1989 17(4) 231-233).
There exists a need for sensitive compositions and methods to detect and measure an internal target non-invasively. Specifically, there exists a need for improved, stable cyanine dyes to detect injuries to various organs that may occur during laparoscopic or robotic surgery. The present invention satisfies these and other needs.